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1.
Int J Mol Sci ; 25(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474092

RESUMO

Proteases are critical enzymes in cellular processes which regulate intricate events like cellular proliferation, differentiation and apoptosis. This review highlights the multifaceted roles of the serine proteases FAM111A and FAM111B, exploring their impact on cellular functions and diseases. FAM111A is implicated in DNA replication and replication fork protection, thereby maintaining genome integrity. Additionally, FAM111A functions as an antiviral factor against DNA and RNA viruses. Apart from being involved in DNA repair, FAM111B, a paralog of FAM111A, participates in cell cycle regulation and apoptosis. It influences the apoptotic pathway by upregulating anti-apoptotic proteins and modulating cell cycle-related proteins. Furthermore, FAM111B's association with nucleoporins suggests its involvement in nucleo-cytoplasmic trafficking and plays a role in maintaining normal telomere length. FAM111A and FAM111B also exhibit some interconnectedness and functional similarity despite their distinct roles in cellular processes and associated diseases resulting from their dysfunction. FAM111A and FAM111B dysregulation are linked to genetic disorders: Kenny-Caffey Syndrome type 2 and Gracile Bone Dysplasia for FAM111A and POIKTMP, respectively, and cancers. Therefore, the dysregulation of these proteases in diseases emphasizes their potential as diagnostic markers and therapeutic targets. Future research is essential to unravel the intricate mechanisms governing FAM111A and FAM111B and explore their therapeutic implications comprehensively.


Assuntos
Doenças do Desenvolvimento Ósseo , Nanismo , Humanos , Peptídeo Hidrolases/genética , Mutação , Proteínas de Ciclo Celular/metabolismo , Nanismo/genética , Endopeptidases/genética , Receptores Virais/metabolismo
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 271-277, 2024 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-38448013

RESUMO

OBJECTIVE: To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. METHODS: Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing. RESULTS: All of the six patients had presented with severe short stature (< 3s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c.5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c.5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c.5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c.5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c.5156G>T was rated as a pathogenic variant (PS2+PM1+PM2_Supporting +PM5+PP3). CONCLUSION: All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.


Assuntos
Doenças do Desenvolvimento Ósseo , Nanismo , Deformidades Congênitas dos Membros , Humanos , Feminino , Animais , Estudos Retrospectivos , Fenótipo , China , Fibrilina-1/genética , Adipocinas
3.
BMC Musculoskelet Disord ; 25(1): 110, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317112

RESUMO

BACKGROUND: Little is known about the progression pattern of vertebral deformities in elderly patients with prevalent vertebral fractures. This population-based cohort study investigated the incidence, progression pattern, and risk factors of vertebral deformity in prevalent vertebral fractures over a finite period of four years in a population-based cohort study. METHODS: A total of 224 inhabitants of a typical mountain village underwent medical examinations every second year from 1997 to 2009, and each participant was followed up for four years. The extent (mild, moderate, severe) and type (wedge, biconcave, crush) of prevalent vertebral fractures on spinal radiographs were evaluated using the Genant semi-quantitative method. Of these participants, 116 with prevalent vertebral fractures at baseline (32 men and 84 women; mean age: 70.0 years) were included in this study. The progression patterns of the 187 vertebral fractures with mild and moderate deformities (except severe deformity) were evaluated. Logistic regression analysis was used to identify the risk factors associated with deformity progression. RESULTS: The progression of vertebral deformities was identified in 13.4% (25 vertebral fractures) of the total 187 prevalent (mild and moderate) vertebral fracture deformities over four years. Among the three deformity types, the prevalence of deformity progression was significantly lower in wedge-type vertebral fractures (P < 0.05). Age and number of prevalent vertebral fractures per participant were independent risk factors associated with the progression of prevalent vertebral deformities. CONCLUSION: This study clarified the natural history of the progression pattern of vertebral deformities in radiographic prevalent vertebral fractures in elderly individuals. Multiple vertebral fractures in the elderly present a risk for the progression of vertebral deformities.


Assuntos
Doenças do Desenvolvimento Ósseo , Fraturas Ósseas , Doenças da Coluna Vertebral , Fraturas da Coluna Vertebral , Masculino , Humanos , Feminino , Idoso , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Estudos de Coortes , Fraturas Ósseas/complicações , Doenças da Coluna Vertebral/complicações , Radiografia , Doenças do Desenvolvimento Ósseo/complicações , Densidade Óssea
4.
JCI Insight ; 9(5)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300707

RESUMO

Geleophysic dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTS-like 2 (ADAMTSL2) variants. It is characterized by distinctive facial features, limited joint mobility, short stature, brachydactyly, and life-threatening cardiorespiratory complications. The clinical spectrum spans from perinatal lethality to milder adult phenotypes. We developed and characterized cellular and mouse models, to replicate the genetic profile of a patient who is compound heterozygous for 2 ADAMTSL2 variants, namely p.R61H and p.A165T. The impairment of ADAMTSL2 secretion was observed in both variants, but p.A165T exhibited a more severe impact. Mice carrying different allelic combinations revealed a spectrum of phenotypic severity, from lethality in knockout homozygotes to mild growth impairment observed in adult p.R61H homozygotes. Homozygous and hemizygous p.A165T mice survived but displayed severe respiratory and cardiac dysfunction. The respiratory dysfunction mainly affected the expiration phase, and some of these animals had microscopic post-obstructive pneumonia. Echocardiograms and MRI studies revealed a significant systolic dysfunction, accompanied by a reduction of the aortic root size. Histology verified the presence of hypertrophic cardiomyopathy with myocyte hypertrophy, chondroid metaplasia, and mild interstitial fibrosis. This study revealed a substantial correlation between the degree of impaired ADAMTSL2 secretion and the severity of the observed phenotype in GD1.


Assuntos
Proteínas ADAMTS , Doenças do Desenvolvimento Ósseo , Deformidades Congênitas dos Membros , Adulto , Humanos , Animais , Camundongos , Proteínas ADAMTS/genética , Doenças do Desenvolvimento Ósseo/genética , Mutação , Fenótipo
5.
Eur J Med Genet ; 68: 104910, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38262577

RESUMO

Lenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features, brachydactyly, symphalangism and cutis laxa. Nineteen cases have been reported in the literature so far, eleven of them with PTDSS1 mutations. Although studies have had clinically similar findings, in some cases the authors have reported even rarer features such as hydrocephalus, facial paralysis, and cleft palate. We, hereby, report the case of the first patient with Lenz-Majewski syndrome (LMS) with molecular confirmation from Turkey. Although our patient had characteristic features described in the literature, she also had immunodeficiency, which has not been reported before. Although there is no established phenotype-genotype correlation, molecular mechanisms can be explained with the reporting of more patients.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Otite Média , Síndrome de Costela Curta e Polidactilia , Feminino , Humanos , Deficiência Intelectual/genética , Doenças do Desenvolvimento Ósseo/genética
6.
Life Sci Alliance ; 7(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38253421

RESUMO

Despite the advances in high-throughput sequencing, many rare disease patients remain undiagnosed. In particular, the patients with well-defined clinical phenotypes and established clinical diagnosis, yet missing or partial genetic diagnosis, may hold a clue to more complex genetic mechanisms of a disease that could be missed by available clinical tests. Here, we report a patient with a clinical diagnosis of Tuberous sclerosis, combined with unusual secondary features, but negative clinical tests including TSC1 and TSC2 Short-read whole-genome sequencing combined with advanced bioinformatics analyses were successful in uncovering a de novo pericentric 87-Mb inversion with breakpoints in TSC2 and ANKRD11, which explains the TSC clinical diagnosis, and confirms a second underlying monogenic disorder, KBG syndrome. Our findings illustrate how complex variants, such as large inversions, may be missed by clinical tests and further highlight the importance of well-defined clinical diagnoses in uncovering complex molecular mechanisms of a disease, such as complex variants and "double trouble" effects.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Anormalidades Dentárias , Humanos , Facies
7.
J Am Acad Orthop Surg ; 32(5): e240-e250, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37852243

RESUMO

INTRODUCTION: Our understanding of the efficacy of guided growth surgery with tension-band plating (TBP) in early-onset Blount disease is evolving. Preliminary work has demonstrated that TBP can normalize the mechanical axis, yet its effect on Langenskiöld stage (LS) has not previously been reported. The primary outcome of this study was improvement in LS after TBP. Secondary outcomes were improvement in LS at most recent follow-up and improvement in mechanical axis deviation (MAD), mechanical medial proximal tibial angle, and mechanical lateral distal femoral angle at treatment completion and most recent follow-up. METHODS: A retrospective review was done of patients with early-onset Blount disease treated with TBP between January 1, 2010, and December 31, 2019, across two institutions. Inclusion criteria were a radiographic diagnosis of early-onset Blount disease (LS changes present), surgery with TBP, and follow-up beyond implant removal. Radiographs before surgery, at removal of hardware (ROH), and at most recent follow-up were evaluated. RESULTS: Twenty-five limbs in 16 children who underwent TBP at a mean age of 5.8 ± 2.3 years were included. Implants were in situ a mean of 1.9 ± 0.7 years. The mean follow-up after ROH was 3.6 ± 1.4 years. LS ranged from 1 to 5 preoperatively with 14 of 25 limbs (56%) staged ≥3. LS improved in 15 of 25 limbs (60%) at ROH and in 21 of 25 limbs (84%) at most recent follow-up. Langenskiöld changes resolved in 7 of 25 limbs (28%) at most recent follow-up. Preoperatively, the MAD was varus in all limbs, but at ROH, the MAD had improved in 22 of 23 limbs with neutral or valgus alignment in 20 of 23 limbs (87%). At most recent follow-up, 16 of 23 limbs (70%) maintained improved alignment. DISCUSSION: There was improvement/resolution of LS and varus deformity in early-onset Blount disease in most patients who underwent TBP. Based on these results, TBP for early-onset Blount disease should be the first-line surgical treatment. LEVEL OF EVIDENCE: IV.


Assuntos
Doenças do Desenvolvimento Ósseo , Osteocondrose/congênito , Criança , Humanos , Pré-Escolar , Estudos Retrospectivos , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/cirurgia , Tíbia/cirurgia , Fêmur/cirurgia
8.
Clin Genet ; 105(3): 313-316, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37990933

RESUMO

We report the case of a 12-year-old girl and her father who both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile-onset hearing loss. The CATSHL (CAmptodactyly - Tall stature - Scoliosis - Hearing Loss syndrome) syndrome was suspected, and molecular analysis revealed a hitherto unreported, monoallelic variant c.1861C>T (p.Arg621Cys) in FGFR3. This variant affects the same residue, but is different than, the variant p.Arg621His reported in the two families with dominant CATSHL described so far. Interestingly, peg-shaped incisors were observed in the proband, a feature never reported in CATSHL but typical of another FGFR3-related condition, LADD (Lacrimo - Auricolo - Dento - Digital) syndrome. The FGFR3 p.Arg621Cys variant seems to be a newly identified cause of CATSHL syndrome with some phenotypic overlap with the LADD syndrome.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Surdez , Deformidades Congênitas da Mão , Perda Auditiva , Doenças do Aparelho Lacrimal , Deformidades Congênitas dos Membros , Escoliose , Sindactilia , Anormalidades Dentárias , Feminino , Humanos , Criança , Escoliose/genética , Perda Auditiva/genética , Síndrome
10.
Eur J Orthop Surg Traumatol ; 34(1): 529-537, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37642701

RESUMO

PURPOSE: The treatment of infantile Blount's disease usually includes surgical correction, but high recurrence is still a problem regardless of the procedure. We conducted a cross-sectional study of severely neglected infantile Blount's disease treated with acute correction and simultaneous hemiepiphysiodesis of lateral proximal tibia physis. In this study, we aimed to observe the complication and recurrence. METHODS: This research is an analytical study with a cross-sectional design using retrospective data collection and total sampling. The subjects were patients with neglected infantile Blount's disease treated from 2018 to 2023 in our institution. Follow-up was conducted in 6, 12, 24, and 36 months. RESULTS: A total of 25 legs from twenty patients were recorded. We observed three legs (12.0%) had recurrence. No neurovascular complications and infections were observed. All subjects had significant postoperative improvement of TFA (mean 6.8 ± 0.730 valgus), Drennan angle, MPTA, MTPD, JLCA, and ligamentous laxity grading (p < 0.001). Lower than 5° postoperative valgus overcorrections and preoperative physeal bar were significant factors in patients with recurrence (p = 0.020 and p = 0.010). There was no significant increase in leg-length discrepancy during follow-up (p = 0.052). There were no significant differences between age, BMI, preoperative TFA, pre- and postoperative Drennan angle, MPTA, MTPD, JLCA, Langenskiöld stages, and length of follow-up in patients with recurrence and not. CONCLUSION: Acute correction with simultaneous hemiepiphysiodesis of lateral proximal tibia physis is an effective technique to prevent deformity recurrence in neglected infantile Blount's disease, provided that the postoperative TFA is more than 5° of valgus and no evidence of physeal bar in the preoperative radiograph.


Assuntos
Doenças do Desenvolvimento Ósseo , Tíbia , Humanos , Tíbia/cirurgia , Estudos Transversais , Estudos Retrospectivos , Resultado do Tratamento , Osteotomia/métodos , Doenças do Desenvolvimento Ósseo/cirurgia
11.
J Pediatr Orthop B ; 33(2): 105-113, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36723665

RESUMO

This study aimed to describe a novel transphyseal osteotomy (TPO) for acute deformity correction in children with bilateral tibia vara and the atraumatic 'slipped proximal tibial epiphysis' (SPTE) entity. We described the clinical and radiological findings in five children (10 limbs) with tibia vara that were treated with the TPO. The criteria for the SPTE were met in nine (9/10) cases. The surgical technique and short-term results of the TPO are reported. The median age was 9 years (range, 6-9), with obesity (BMI > 95th centile) present in all children. The medial tibial plateau was not significantly depressed (the median angle of depression of the medial plateau measured 30° (range, 20°-32°). The mean medial proximal tibial angle of 33° (range, 8°-71°) was corrected to 82° (range, 77°-86°), the mean anatomic posterior proximal tibial angle of 48° (range, 32°-70°) was corrected to 72° (range, 61°-86°), and the median internal tibial rotation of 45° (range, 20°-50° internal rotation) was corrected to neutral rotation (range, 10° internal-10° external rotation). There were two complications: one case of recurrent deformity and one case of intra-articular extension of the osteotomy. We describe a novel TPO that aims to simultaneously correct all aspects of the deformity, stabilise the physis, and prevent recurrence through epiphysiodesis. Further research is required to determine its efficacy and safety. The atraumatic SPTE appears to represent a specific morphological presentation in tibia vara. Level of evidence: 4.


Assuntos
Doenças do Desenvolvimento Ósseo , Osteocondrose/congênito , Tíbia , Criança , Humanos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/cirurgia , Osteotomia/métodos , Epífises/diagnóstico por imagem , Epífises/cirurgia
12.
J Arthroplasty ; 39(3): 645-650, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37757984

RESUMO

BACKGROUND: This study aimed to investigate the clinical outcomes of fixed-bearing medial unicompartmental knee arthroplasty (UKA) for tibia vara knees and the associated changes in joint space malalignment (JSM) and joint line obliquity (JLO). METHODS: We retrospectively analyzed a consecutive group of 100 patients who underwent fixed-bearing medial UKA with a preoperative medial proximal tibia angle (MPTA) ≥86° (n = 50) and MPTA <86° (n = 50) and who had a minimum 5-year follow-up. Radiological parameters, including the hip-knee-ankle angle, MPTA, and the postoperative JSM and JLO, were measured. Functional evaluation was performed using the range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The MPTA <86° group showed significantly higher postoperative JLO (91.8 versus 90.4°, respectively; P = .002) and JSM (6.1 versus 4.2°, respectively; P = .026) compared to the MPTA ≥86° group. Functional outcomes, including range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores, were not significantly different between the 2 groups. CONCLUSIONS: Fixed-bearing medial UKA is a safe and effective surgical option for patients who have tibia vara knees, as an increase in JLO and JSM postoperatively does not have a clinically relevant impact, even after a minimum 5-year follow-up.


Assuntos
Artroplastia do Joelho , Doenças do Desenvolvimento Ósseo , Osteoartrite do Joelho , Osteocondrose/congênito , Humanos , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Seguimentos , Estudos Retrospectivos , Articulação do Joelho/cirurgia , Tíbia/cirurgia
13.
Genet Med ; 26(3): 101050, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38126281

RESUMO

PURPOSE: Hao-Fountain syndrome (HAFOUS) is a neurodevelopmental disorder caused by pathogenic variants in USP7. HAFOUS is characterized by developmental delay, intellectual disability, speech delay, behavioral abnormalities, autism spectrum disorder, seizures, hypogonadism, and mild dysmorphic features. We investigated the phenotype of 18 participants with HAFOUS and performed DNA methylation (DNAm) analysis, aiming to generate a diagnostic biomarker. Furthermore, we performed comparative analysis with known episignatures to gain more insight into the molecular pathophysiology of HAFOUS. METHODS: We assessed genomic DNAm profiles of 18 individuals with pathogenic variants and variants of uncertain significance (VUS) in USP7 to map and validate a specific episignature. The comparison between the USP7 cohort and 56 rare genetic disorders with earlier reported DNAm episignatures was performed with statistical and functional correlation. RESULTS: We mapped a sensitive and specific DNAm episignature for pathogenic variants in USP7 and utilized this to reclassify the VUS. Comparative epigenomic analysis showed evidence of HAFOUS similarity to a number of other rare genetic episignature disorders. CONCLUSION: We discovered a sensitive and specific DNAm episignature as a robust diagnostic biomarker for HAFOUS that enables VUS reclassification in USP7. We also expand the phenotypic spectrum of 9 new and 5 previously reported individuals with HAFOUS.


Assuntos
Anormalidades Múltiplas , Transtorno do Espectro Autista , Doenças do Desenvolvimento Ósseo , Anormalidades Craniofaciais , Surdez , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Humanos , Metilação de DNA/genética , Transtorno do Espectro Autista/genética , Peptidase 7 Específica de Ubiquitina/genética , Epigenômica , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Biomarcadores
14.
J Pediatr Orthop ; 44(4): 254-259, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38158726

RESUMO

BACKGROUND: Blount disease can occur at any time during the growth process, primarily with a bimodal distribution in children younger than 4 years old and adolescents. The disease process most commonly presents in Black adolescents, with disease severity positively correlated with obesity. Given the known associations among race, obesity, and socioeconomic status, we investigated the relationship between the degree of social deprivation and severity of lower extremity deformities among a community-based cohort with Blount disease. METHODS: A retrospective review of hospital records and radiographs of patients with previously untreated Blount disease was conducted. Patients were classified as having early-onset or late-onset Blount disease based on whether the lower limb deformity was noted before or after the age of 4 years. The area deprivation index (ADI), a nationally validated measure that assesses socioeconomic deprivation by residential neighborhood, was calculated for each patient as a surrogate for socioeconomic status. Higher state (range: 1 to 10) or national (range: 1 to 100) ADI corresponds to increased social deprivation. Full-length standing radiographs from index clinic visits were evaluated by 2 reviewers to measure frontal plane deformity. The association of ADI with various demographic and radiographic parameters was then analyzed. RESULTS: Of the 65 patients with Blount disease, 48 (74%) children were Black and 17 (26%) were non-black children. Nineteen children (32 limbs) had early-onset and 46 children (62 limbs) had late-onset disease. Black patients had significantly higher mean state (7.6 vs. 5.4, P =0.009) and national (55.1 vs. 37.4, P =0.002) ADI values than non-black patients. Patients with severe socioeconomic deprivation had significantly greater mechanical axis deviation (66 mm vs. 51 mm, P =0.008). After controlling demographic and socioeconomic factors, the results of multivariate linear regression showed that only increased body mass index (ß=0.19, 95% CI: 0.12-0.26, P <.001) and state ADI (ß=0.021, 95% CI: 0.01-0.53, P =.043) were independently associated with greater varus deformity. CONCLUSIONS: Socioeconomic deprivation was strongly associated with increased severity of varus deformity in children with late-onset Blount disease. Our analysis suggests that obesity and socioeconomic factors are the most influential with regard to disease progression. LEVEL OF EVIDENCE: Level III.


Assuntos
Doenças do Desenvolvimento Ósseo , Osteocondrose/congênito , Criança , Adolescente , Humanos , Pré-Escolar , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/epidemiologia , Estudos Retrospectivos , Obesidade , Fatores Socioeconômicos
15.
Pediatr Neurol ; 151: 138-142, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38157719

RESUMO

BACKGROUND: KBG syndrome is a genetic disorder characterized by short stature, dysmorphic features, macrodontia, cognitive impairment, and limb anomalies. Epilepsy is an important comorbidity associated with KBG syndrome, although the entire phenotypic spectrum may not be fully appreciated. METHODS: We identified five new patients with KBG syndrome-related epilepsy and compared their phenotype to previously reported cases in the literature. RESULTS: Five patients with KBG syndrome-related epilepsy were identified. Three patients (60%) were male. Median age of seizure onset was 18 months (interquartile range 5, 32). The epilepsy type was generalized in three patients (60%); in two, the epilepsy type was combined (40%), with focal and generalized seizures. In one patient (20%), the epilepsy syndrome was classifiable and the child was diagnosed with myoclonic-atonic epilepsy. All five patients had pathogenic variants in the ANKRD11 gene. Epilepsy was refractory in two patients (40%). No specific antiseizure medication (ASM) was found to be superior. Literature review yielded 134 cases, median age of seizure onset was 4 years, and seizures were generalized (n = 60, 44%), focal (n = 26, 19%), or combined (n = 13, 10%). An epilepsy syndrome was diagnosed in 12 patients (8.8%). In those with documented response to ASM (n = 49), 22.4% were refractory (n = 11). CONCLUSIONS: Our study confirms that few patients with epilepsy and KBG syndrome have an identifiable epilepsy syndrome and generalized seizures are most common. We highlight that epilepsy associated with KBG syndrome may occur before age one year and should be an important diagnostic consideration in this age group.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Epilepsias Mioclônicas , Epilepsia , Deficiência Intelectual , Anormalidades Dentárias , Criança , Humanos , Masculino , Lactente , Pré-Escolar , Feminino , Anormalidades Múltiplas/diagnóstico , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico , Doenças do Desenvolvimento Ósseo/diagnóstico , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética , Facies , Proteínas Repressoras/genética , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Convulsões/genética , Fenótipo
17.
J Dent Child (Chic) ; 90(3): 168-172, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38123928

RESUMO

Segmental odontomaxillary dysplasia (SOD) is an uncommon and likely underrecognized developmental condition. In rare cases, SOD can also result in anomalies of the ipsilateral mandibular alveolar process and teeth. This report presents two cases of SOD with mandibular involvement to highlight this potential variation in SOD presentation. These cases help shed new light on our understanding of the disease mechanism and pathoetiology, while also informing clinicians to be diligent in imaging the ipsilateral mandible for dental anomalies in their patients with SOD. Based on the involvement of both jaws, the name change to 'segmental ipsilateral odontognathic dysplasia' is justified to better reflect its pathophysiology.


Assuntos
Doenças do Desenvolvimento Ósseo , Má Oclusão , Odontodisplasia , Anormalidades Dentárias , Humanos , Mandíbula/diagnóstico por imagem , Maxila/anormalidades , Odontodisplasia/diagnóstico por imagem
18.
Otol Neurotol ; 44(10): 1082-1085, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37939359

RESUMO

OBJECTIVE: We document the first successful transmastoid surgical treatment of facial nerve palsy for a patient with craniometaphyseal dysplasia (CMD), a rare genetic disease. PATIENT: A 9-month-old girl with bilateral facial nerve palsies and conductive hearing loss. Genetic testing made a diagnosis of CMD, and imaging showed narrowing of the facial nerve canals and ossicular fixation. INTERVENTION: Right transmastoid facial nerve decompression and ossicular chain reconstruction. MAIN OUTCOME MEASURE: Facial nerve function (House-Brackmann grade). RESULTS: Facial nerve function initially worsened, then improved within 12 months from House-Brackmann grade IV-V to grade III. CONCLUSION: Surgical cranial nerve decompression of and ossicular chain reconstruction may be effective treatments for patients with CMD.


Assuntos
Doenças do Desenvolvimento Ósseo , Paralisia Facial , Feminino , Humanos , Lactente , Nervo Facial/cirurgia , Paralisia Facial/etiologia , Paralisia Facial/cirurgia , Paralisia Facial/diagnóstico , Doenças do Desenvolvimento Ósseo/cirurgia , Resultado do Tratamento , Descompressão Cirúrgica/métodos , Estudos Retrospectivos
19.
Sci Rep ; 13(1): 18528, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37898650

RESUMO

Type II rickets is a hereditary disease caused by a mutation in the vitamin D receptor (VDR) gene. The main symptoms of this disease are bone dysplasia and alopecia. Bone dysplasia can be ameliorated by high calcium intake; however, there is no suitable treatment for alopecia. In this study, we verified whether gene therapy using an adenoviral vector (AdV) had a therapeutic effect on alopecia in Vdr-KO rats. The VDR-expressing AdV was injected into six 7-week-old female Vdr-KO rats (VDR-AdV rats). On the other hand, control-AdV was injected into 7-week-old female rats (control-AdV rats); non-infected Vdr-KO rats (control rats) were also examined. The hair on the backs of the rats was shaved with hair clippers, and VDR-AdV or control-AdV was intradermally injected. Part of the back skin was collected from each rat after AdV administration. Hair follicles were observed using hematoxylin and eosin staining, and VDR expression was examined using immunostaining and western blotting. VDR-AdV rats showed significant VDR expression in the skin, enhanced hair growth, and low cyst formation, whereas control-AdV and non-infected rats did not show any of these effects. The effect of VDR-AdV lasted for nearly 60 days. These results indicate that gene therapy using VDR-AdV may be useful to treat alopecia associated with type II rickets, if multiple injections are possible after a sufficient period of time.


Assuntos
Doenças do Desenvolvimento Ósseo , Raquitismo , Feminino , Ratos , Animais , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Alopecia/genética , Alopecia/terapia , Alopecia/complicações , Terapia Genética , Adenoviridae/genética , Adenoviridae/metabolismo , Vitamina D/uso terapêutico
20.
Medicine (Baltimore) ; 102(40): e35449, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800809

RESUMO

RATIONALE: KBG syndrome (KBGS, OMIM: 148050), a rare genetic disorder, is clinically characterized by megalodontia, short stature, skeletal abnormalities, and nervous system manifestations. In the study, we explore the clinical and genetic characteristics of one neonate suffering KBGS caused by ANKRD11 gene mutation. PATIENT CONCERNS: The proband, a female, was born prematurely at 31 + 2 weeks. There were repeated infections and abdominal distension in the first month after birth, and the platelets could not rise to normal. Head ultrasound showed intracranial brain injury and intracranial hemorrhage. DIAGNOSES: Sequencing revealed that there was a heterozygous mutation in exon 9 of the ANKRD11 gene (NM_013275.5) for the child, c.1896_1897delTA (p.H632Qfs*30), which was a de novo mutation and has not been reported. Combining clinical features and genetic results, the proband was diagnosed as KBGS. INTERVENTIONS AND OUTCOMES: The brain sonography on day 4 after birth showed brain injury and intracranial hemorrhage. Therefore, 140 mg of bovine lung surfactant was administered through endotracheal intubation in addition to ventilator-assisted ventilation. Antibiotic treatment was also given till the inflammatory indicators of the infant returned to normal levels. The following-up of 1-year-6-month showed that the language, motion and height of development is slight falling behind the children of the same age. LESSONS: This is the first case of KBGS was diagnosed in the neonatal period, which provides a reference for the child to receive timely and correct treatment.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Lesões Encefálicas , Deficiência Intelectual , Anormalidades Dentárias , Feminino , Humanos , Recém-Nascido , Anormalidades Múltiplas/diagnóstico , Doenças do Desenvolvimento Ósseo/diagnóstico , Facies , Deficiência Intelectual/genética , Hemorragias Intracranianas , Mutação , Fenótipo , Anormalidades Dentárias/diagnóstico
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